DESCRIPTION: As background to this project, the PI states that plasmid DNA vaccination is proving to be a powerful approach for eliciting antibody. TH1 and cytotoxic CTL responses in small laboratory animals and nonhuman primates. With this as background the PI plans 5 specific aims utilizing primate and mouse systems to characterize immune responses and states that he will explore novel applications of this technology for the development of an HIV-1 vaccine. Specifically. The PI will explore the delivery of plasmid IL-I5/Ig DNA to augment plasmid DNA vaccine-elicited immunity to HIV-l Env. This study will be similar to the above primate study but will concentrate on the mouse model. Based on the similarity of IL-15 to IL-2 the PI proposes to further explore the use of IL-15-Ig in immune expansion of plasmid induced immune responses. This study will also explore the use of B7.1 and B7.2 as DNA constructs in immune response induction by DNA vaccines. (1) Use of IL-2/Ig as a protein or DNA plasmid to augment plasmid DNA vaccine- elicited HIV-l Env specific immunity. This study will focus on co delivery of Ig fusion proteins as expression cassettes for cytokine gene along with an env DNA vaccine encoding gp120. This study is planned for the macaque system. (2) Delivery of plasmid IL-I5/Ig DNA to augment plasmid DNA vaccine-elicited immunity to HIV-l Env. This study will be similar to the above primate study but will concentrate on the mouse model. Based on the similarity of IL-15 to IL-2 the PI proposes to further explore the use of IL-15-Ig in immune expansion of plasmid induced immune responses. This study will also explore the use of B7.1 and B7.2 as DNA constructs in immune response induction by DNA vaccines. (3) Efficacy of plasmid SIVmac gag DNA vaccine priming for induction of secondary Gag-specific CTL responses. This study will focus on the use of a new construct, Siv mac gag. The ability of this construct to induce cellular immune response in the Mau-A01 system will be studied. (4) Elicitation of CTL specific for a broad range of codominant epitopes using plasmid DNA vaccination. This study will through the use of a construct that deletes the mauA1 CTL epitope will seek to determine the ability of this approach to induce CTL responses to sub dominant epitopes. Challenges are planned as part of this aim. (5) Use of IL-2/Ig as a protein or DNA plasmid to augment plasmid DNA vaccine- elicited HIV-l Env specific immunity. This study will focus on co delivery of Ig fusion proteins as expression cassettes for cytokine genes along with an env DNA vaccine encoding gp120. This study is planned for the macaque system. (5) Elicitation of CTL specific for a broad range of codominant epitopes using plasmid DNA vaccination. This study will through the use of a construct that deletes the mauA1 CTL epitope will seek to determine the ability of this approach to induce CTL responses to sub dominant epitopes. Challenges are planned as part of this aim. (6). Utility of plasmid DNA vaccination to broaden CTL recognition of variant viruses. Using a pool of peptides including the dominant p11C epitope as well as 6 peptide variants which bind to the Mau A1 epitope, the ability of the gag vaccine to induce such cross reactive responses to these peptide variants will be studied. This aim therefore studies cross reactivity to a single epitope not multi epitopes.